Sirtuin1 (Sirt1) is an unusual target for aging and aging-associated diseases. During the screening for Sirt1 activators from natural compounds, piperlongumine (PL), one of the major constituents of Piper longum, potently activated the deacetylase ability of Sirt1 in vitro. Treatment with PL, which regulated the gene transcription of antioxidant response element in hippocampal neurons, attenuated the cytotoxicity induced by intraneuronal Aβ_1-42 expression. The oral administration of PL, at a dose of 50 mg/kg/day for 2.5 months, significantly reduced the occupied area of beta-amyloid in parietal cortex of APP/PS1 mice. Novel object recognition and working memory impairment also markedly improved. Moreover, activated microglia and astrocytes in the cortex notably decreased, indicating the anti-inflammatory activity of PL. Finally, vesicular glutamate transporter 1 significantly increased in the hippocampus of APP/PS1 mice following PL treatment. These results suggested the beneficial effects PL and its therapeutic potential to ameliorate AD-like pathology.

Sirtuin1（Sirt1）是衰老和衰老相关疾病的不寻常靶标。在从天然化合物中筛选出Sirt1活化剂的过程中，长笛胡椒的主要成分之一哌啶隆敏（PL）在体外有效地激活了Sirt1的脱乙酰酶能力。PL处理可调节海马神经元中抗氧化反应元件的基因转录，从而减轻神经元内_Aβ1-42诱导的细胞_毒性表达。以50 mg / kg / day的剂量口服PL，持续2.5个月，可显着减少APP / PS1小鼠顶叶皮层中β淀粉样蛋白的占据面积。新型对象识别和工作记忆障碍也得到明显改善。此外，皮层中活化的小胶质细胞和星形胶质细胞明显减少，表明PL的抗炎活性。最后，PL处理后，APP / PS1小鼠海马中的囊状谷氨酸转运蛋白1显着增加。这些结果表明PL的有益作用及其改善AD样病理的治疗潜力。